Description: (Taken directly from the application) By any measure, during the first funding period (1994-present) it is believed that CORE A of the Center of Excellence achieved its stated goals and had an enormous impact on the Harvard Medical Area?s efforts in using the newer methods of mouse genetics to dissect hematological problems. Indeed, CORE A is an irreplaceable resource within the Harvard/Boston hematology community. As an added benefit, the Center mechanism has been instrumental in facilitating rapid development of instructor level and junior faculty. For example, the generation of mice for E. Neufeld and N. Andrews occurred at a critical time in the establishment of their independent laboratories within CH. The production of mice for two instructors at the DFCI, J. Friedman and C. Twist, provided these individuals the opportunity to obtain invaluable reagents at a time in their research careers when they could not have done so themselves. With further support the Principal Investigator intends to maintain CORE A as a resource for the Harvard/Boston hematology community and expand the overall impact of its activities in new directions. The Specific Aims are the following: Specific Aims: 1. Continue to assist in the generation of gene targeted mice for the Principal Investigator?s laboratory (to complement existing NIH and HHMI funding). 2. Generate gene targeted ES cells and mice, and provide advice and assistance in the analysis of hematopoiesis in mice, Center members (non-exclusive) 3. Develop, test, and use reagents for conditional gene targeting in mice, and provide these to investigators at other sites (US or worldwide) To achieve these goals the personnel of CORE A will need to be increased as reflected in the budget provided elsewhere. Because of the increased demands on current personnel in the maintenance and breeding of existing and planned mouse strains, an additional technician dedicated to mouse husbandry is required. In order to facilitate generation of gene targeted ES cells and provide training to other investigators affiliated with the Center, it may become necessary in the future to hire a full-time technician who will be responsible for cell culture, preparation of genomic DNA of selected ES cell clones, and Southern blot analysis of DNA for detection of targeted clones. Finally, given frequent assistance requested of CORE A in the planning, construction, and use of targeting constructs and the efforts devoted to technology development for conditional gene targeting largely based within the Center, we have requested partial support for a Ph. D. fellow within CORE A. We believe that this increase in personnel will consolidate CORE A and permit it to function more efficiently for the Center?s members and become more autonomous of activities of the Principal Investigator?s laboratory. It will also have the added benefit of reducing the demands on the Principal Investigator?s time for consulting with investigators regarding their specific gene targeting projects and mouse analysis.